Abstract:
Context.—Burkitt lymphoma (BL) is histologically char-
acterized by a ‘‘starry sky’’ appearance, representing scat-
tered macrophages that have phagocytosed cell debris
among proliferating lymphoma cells. As is well known, al-
most all the neoplastic cells of endemic BL are infected
with Epstein-Barr virus (EBV). Previous studies have indi-
cated that most of the EBV in B cells is latent, and few
virus particles enter the lytic cycle.Objective.—To examine the histologic relationship be-
tween EBV infection stages and the formation of the starry
sky pattern in African endemic BL tissues.Design.—Tissue samples from 44 patients with African
endemic BL were examined with immunohistochemistry
and in situ hybridization. We used EBV-encoded small RNA
(EBER) as a marker of latent infection, and
BamHI H left
frame 1 (BHLF1) and
BamHI Z EBV replication activator
(ZEBRA) as lytic cycle markers.Results.—In all cases, signals for EBER were found in
most neoplastic lymphocytes, and in 73% of cases, signals
for BHLF1 and/or ZEBRA were recognized in the lympho-
ma cells within and around the lacunae in starry sky fig-
ures. The mean number of lacunae per unit area in cases
positive for lytic cycle markers was significantly higher
than that in negative cases (
P , .001).
Conclusions.—Our findings suggest that EBV-infected
lymphoma cells in the lytic cycle, which eventually lapse
into cell death, are phagocytosed prior to their rupture by
macrophages that have migrated into the parenchyma. We
emphasize that transition of EBV-infected lymphoma cells
to the lytic cycle is one of the histomorphogenetic factors
influencing the formation of starry sky pattern in endemic
BL.
